Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

Early HHV-6 reactivation increases the risk of graft rejection after haploidentical hematopoietic cell transplantation

Bone Marrow Transplantation volume 60, pages 1292–1295 (2025)Cite this article

Subjects

Access through your institution
Buy or subscribe

Viral reactivations remain common complications after hematopoietic cell transplantation (HCT). The role of cytomegalovirus, Epstein-Barr virus, or adenovirus infection/reactivation has been frequently analyzed and discussed, whereas the impact of human herpesvirus-6 (HHV-6) on transplant outcome is still a matter of debate [1, 2].

We retrospectively analyzed 340 pediatric patients (Supplemental Table 1), who underwent HCT from matched family (17%), matched unrelated (43%), or haploidentical family donors (40%) between 2012 and 2021, to estimate the incidence of HHV-6 reactivation, identify risk factors, and assess its impact on outcomes.

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Analysis of HHV6 reactivation and transplant outcomes according to the time of HHV-6 reactivation in the cohort.

References

  1. Ward KN, Hill JA, Hubacek P, de la Camara R, Crocchiolo R, Einsele H, et al. Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation. Haematologica. 2019;104:2155–63. https://doi.org/10.3324/haematol.2019.223073.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Zerr DM, Boeckh M, Delaney C, Martin PJ, Xie H, Adler AL, et al. HHV-6 reactivation and associated sequelae after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18:1700–8. https://doi.org/10.1016/j.bbmt.2012.05.012.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Watzinger F, Suda M, Preuner S, Baumgartinger R, Ebner K, Baskova L, et al. Real-time quantitative PCR assays for detection and monitoring of pathogenic human viruses in immunosuppressed pediatric patients. J Clin Microbiol. 2004;42:5189–98. https://doi.org/10.1128/JCM.42.11.5189-5198.2004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Perruccio K, Sisinni L, Perez-Martinez A, Valentin J, Capolsini I, Massei MS, et al. High incidence of early human herpesvirus-6 infection in children undergoing haploidentical manipulated stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2018;24:2549–57. https://doi.org/10.1016/j.bbmt.2018.07.033.

    Article  PubMed  Google Scholar 

  5. Miura H, Kawamura Y, Hattori F, Tanaka M, Kudo K, Ihira M, et al. Human herpesvirus-6B infection in pediatric allogenic hematopoietic stem cell transplant patients: Risk factors and encephalitis. Transpl Infect Dis. 2020;22:e13203 https://doi.org/10.1111/tid.13203.

    Article  PubMed  Google Scholar 

  6. Greco R, Crucitti L, Noviello M, Racca S, Mannina D, Forcina A, et al. Human herpesvirus 6 infection following haploidentical transplantation: immune recovery and outcome. Biol Blood Marrow Transplant. 2016;22:2250–5. https://doi.org/10.1016/j.bbmt.2016.09.018.

    Article  PubMed  Google Scholar 

  7. Han TT, Zhang YN, Sun YQ, Kong J, Wang FR, Wang ZD, et al. Human herpesvirus 6 reactivation in unmanipulated haploidentical hematopoietic stem cell transplantation predicts the occurrence of grade II to IV acute graft-versus-host disease. Transpl Infect Dis. 2021;23:e13544. https://doi.org/10.1111/tid.13544.

    Article  PubMed  CAS  Google Scholar 

  8. Oltolini C, Greco R, Galli L, Clerici D, Lorentino F, Xue E, et al. Infections after allogenic transplant with post-transplant cyclophosphamide: impact of donor HLA matching. Biol Blood Marrow Transplant. 2020;26:1179–88. https://doi.org/10.1016/j.bbmt.2020.01.013.

    Article  PubMed  Google Scholar 

  9. Noviello M, Lorentino F, Xue E, Racca S, Furnari G, Valtolina V, et al. Human herpesvirus 6-specific T-cell immunity in allogeneic hematopoietic stem cell transplant recipients. Blood Adv. 2023;7:5446–57. https://doi.org/10.1182/bloodadvances.2022009274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Dulery R, Salleron J, Dewilde A, Rossignol J, Boyle EM, Gay J, et al. Early human herpesvirus type 6 reactivation after allogeneic stem cell transplantation: a large-scale clinical study. Biol Blood Marrow Transplant. 2012;18:1080–9. https://doi.org/10.1016/j.bbmt.2011.12.579.

    Article  PubMed  Google Scholar 

  11. Phan TL, Carlin K, Ljungman P, Politikos I, Boussiotis V, Boeckh M, et al. Human herpesvirus-6B reactivation is a risk factor for grades II to IV acute graft-versus-host disease after hematopoietic stem cell transplantation: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2018;24:2324–36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Betts BC, Young JA, Ustun C, Cao Q, Weisdorf DJ. Human herpesvirus 6 infection after hematopoietic cell transplantation: is routine surveillance necessary? Biol Blood Marrow Transplant. 2011;17:1562–8. https://doi.org/10.1016/j.bbmt.2011.04.004.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was partly supported by the Ministry of Health, Ricerca Corrente (08045823 to MZ, 08069119 to PC).

Author information

Author notes

  1. These authors contributed equally: Patrizia Comoli, Marco Zecca.

Authors and Affiliations

  1. Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Francesca Compagno, Stella Boghen, Tommaso Mina, Arianna Panigari, Annalisa Agostini, Giovanna Giorgiani & Marco Zecca

  2. Cell Factory, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Marika De Cicco, Stella Muscianisi, Jennifer Zumelli & Patrizia Comoli

  3. Immunohaematology and Transfusion Service, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

    Claudia Del Fante & Cesare Perotti

  4. Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

    Fausto Baldanti

  5. Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

    Fausto Baldanti & Stefania Paolucci

Authors
  1. Francesca Compagno
    View author publications

    Search author on:PubMed Google Scholar

  2. Stella Boghen
    View author publications

    Search author on:PubMed Google Scholar

  3. Tommaso Mina
    View author publications

    Search author on:PubMed Google Scholar

  4. Arianna Panigari
    View author publications

    Search author on:PubMed Google Scholar

  5. Annalisa Agostini
    View author publications

    Search author on:PubMed Google Scholar

  6. Marika De Cicco
    View author publications

    Search author on:PubMed Google Scholar

  7. Stella Muscianisi
    View author publications

    Search author on:PubMed Google Scholar

  8. Jennifer Zumelli
    View author publications

    Search author on:PubMed Google Scholar

  9. Claudia Del Fante
    View author publications

    Search author on:PubMed Google Scholar

  10. Cesare Perotti
    View author publications

    Search author on:PubMed Google Scholar

  11. Giovanna Giorgiani
    View author publications

    Search author on:PubMed Google Scholar

  12. Fausto Baldanti
    View author publications

    Search author on:PubMed Google Scholar

  13. Stefania Paolucci
    View author publications

    Search author on:PubMed Google Scholar

  14. Patrizia Comoli
    View author publications

    Search author on:PubMed Google Scholar

  15. Marco Zecca
    View author publications

    Search author on:PubMed Google Scholar

Contributions

FC, PC and MZ wrote the manuscript and were involved in all aspects of the project including research design, manuscript preparation, and analyzing experimental and clinical data; SB, TM, AP, AA, CDF CP and GG were responsible for the clinical management of the patients and helped to collect clinical and laboratory data; MDC, SM and JZ helped with sample preparation and were responsible for the laboratory tests; SP and FB were responsible for all the virological analyses; all authors critically reviewed and approved the manuscript.

Corresponding author

Correspondence to Marco Zecca.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Compagno, F., Boghen, S., Mina, T. et al. Early HHV-6 reactivation increases the risk of graft rejection after haploidentical hematopoietic cell transplantation. Bone Marrow Transplant 60, 1292–1295 (2025). https://doi.org/10.1038/s41409-025-02641-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41409-025-02641-y

Search

Advanced search

Quick links